Drugs for Epilepsy Flashcards
4 components of Seizures
- are periods of neural hyper-excitation
- the forebrain begin to fire in massive synchronized bursts
- Blood flow to the brain is increased
- greater use of glucose & oxygen
Prevalence of epilepsy
lifetime prevalence of about 4 %
Epilepsy/ seizure disorder
the epilepsies are a group of neurological disorders characterised by spontaneous, recurrent seizures People with epilepsy have a low seizure threshold
Causes of epilepsy
Genetic (70%)
Structural/ metabolic (30%)
Common structural cases of epilepsy
brain scars, cancer/ benign tumor, vascular malformation
Onset of Epilepsy
In many patients seizures begin in childhood, often before the age of 15 years.
Children with epilepsy will sometimes “outgrow” seizures or will have reduced frequency of seizures in adulthood.
Comorbidities of epilepsy
- Cognitive – memory problems
- Psychiatric – anxiety, depression, ADHD, psychosis
- Also co-morbidities for asthma, migraine, stroke, ulcers
Generalized Seizures
Occur throughout the cortex
Partial Seizures
Occur in just one location of the cortex
2 Types of Partial seizures
- Simple partial
- Complex Partial
2 Types of Generalized seizures
- Absence
- Tonic Clonic
Absence (petit mal) Seizures
- (do not usually cause lasting damage)
- Briefly unconscious, blank stare, no memory of attack (not aware that they had seizure)
- Lasts less than 30 seconds
- 3 per second spike and wave throughout whole brain
Tonic Clonic (grand mal)
- occur less frequently than absence
- Unconscious, dramatic convulsions, no memory of attack
- Lasts less than 5 minutes
- Constant spiking throughout the whole brain
status epilepticus
a seizure that lasts more than 5 mins
Simple partial
- Conscious, memory of attack, sensory/motor/emotion symptoms
- Duration varies
- Localized spiking in neocortical or limbic area of brain
Complex partial (temporal lobe)
- Conscious but non-responsive, automatisms, no memory of attack (temporal lobe)
- Duration varies
- Localized then spreading spiking in one or both temporal lobes
- Hippocampus is involved & patient has no memory of seizure
Normal EEG Pattern
Low voltage, asynchronized
EEG during absence seizure
Looks similar to delta wave pattern (these seizures are generated in the thalamus)
EEG during tonic-clonic seizure
Asynchronous high voltage firing- period after seizure (brain recovering)- not a lot of firing
Anti-seizure medications generally act by…
promoting GABA signaling or reducing the function of voltage gated ion channels
Treatment for epilepsy
- A diet low in carbohydrates causes the body to metabolize fats into ketones (Ketogenic diet)
Common side effects of anti-seizure medications
sleepiness, memory impairment, nausea/GI upset, dependence/withdrawal
Consequences if Epilepsy is not managed
- Permanent brain damage
- Seizure worsening- death from seizures
- Difficulty learning
- breathing in food or saliva into the lungs during a seizure, which can cause aspiration pneumonia
With excess amount of calcium
Neuron dies
Phenobarbital (Luminal)
- a barbituate
- First drug for tonic-clonic and partial seizures
- Oldest drug still in use
- long half-life
- cheap
Mechanism of Phenobarbital
enhances GABA-A system – keeps the GABA channel open longer – increases the inhibitory effect of GABA
Phenytoin (Dilantin)
- Second drug for tonic-clonic and partial seizures
- less sedating than phenobarbital, also has long half-life
- Second oldest drug still in use
Mechanism of Phenytoin
Blocks voltage dependent sodium channels (antagonist)
- Phenytoin blocks the channels and reduces the number of action potentials that a neuron can fire
Ethosuximide (Zarontin)
The drug of choice for absence seizures
Mechanism of Ethosuximide
Blocks voltage dependent calcium channels (antagonist)
- blocks one specific type of these calcium channels that is found in the thalamus and reduces the amount of glutamate neurotransmitter that is released in that brain region
Carbamazepine (Tegretol)
- A treatment for tonic-clonic and partial seizures.
- also used to treat bipolar disorder
Mechanism of Carbamazepine
Blocks voltage dependent sodium channels (antagonist)
- blocks the channels and reduces the number of action potentials that a neuron can fire. It has a mechanism of action similar to phenytoin but they have different side effects
Valproate (Valproic acid) (Depakene)
- The first broad-spectrum drug – effective for absence, tonic-clonic, and partial seizures
- Used to treat bipolar disorder
Mechanism of Valproate
Multiple and not fully understood.
- 1st MOA - Blocks voltage dependent sodium channels (antagonist). In this way it is similar to phenytoin and carbamazepine.
- 2nd MOA – opens up chromatin/DNA structure to allow more gene expression = epigenetics. One of genes that is expressed is for enzyme that makes GABA – more GABA = more inhibition of neuron firing
GRIN1 Disorder/ Features of GRIN1 Encephalopathy
- Motor impairments – hypotonia, dystonia, hyperkinesis
- Cortical visual impairment (CVI) is reported for many patients
- Oculogyric crisis – abnormal eye movements – also associated with GLUT1 deficiency syndrome
